TMA7B (Translation machinery-associated protein 7B) is a small 64-amino acid protein belonging to the TMA7 family (Pfam: PF09072, InterPro: IPR015157). It is a paralog of human TMA7 (Q9Y2S6). No direct experimental studies characterize human TMA7B specifically; however, function can be inferred from the well-characterized yeast ortholog TMA7 (Saccharomyces cerevisiae). In yeast, TMA7 associates with the 40S ribosomal subunit in an EDTA-sensitive manner and is required for efficient cytoplasmic translation. Yeast tma7-null mutants show approximately 95% reduction in protein synthesis (35S-methionine incorporation), reduced polysomes relative to monosomes (indicative of a translation initiation defect), and resistance to the translation inhibitor anisomycin [PMID:16702403]. Cross-species complementation studies demonstrate functional conservation of TMA7 family members across eukaryotes, as human MCT-1 (TMA20 homolog) can rescue yeast tma20 defects [PMID:16702403]. Recent mammalian proteomics studies link TMA7 family protein levels to ribosome quality control pathways (Luo et al. 2023 bioRxiv). Plant ribosome proteomics also identified the Arabidopsis TMA7 homolog co-purifying with 80S cytosolic ribosomes (Salih et al. 2019 bioRxiv), supporting conserved ribosome association across eukaryotes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043022 ribosome binding | ISS PMID:16702403 Systematic identification and functional screens of uncharac... | NEW | Summary: Ribosome binding is inferred from yeast TMA7 ortholog evidence. Yeast TMA7 shows EDTA-dependent cosedimentation with ribosomes (particularly 40S subunit) in sucrose gradients [PMID:16702403]. This term better reflects the evidence than "structural constituent of ribosome" since TMA7 is an associated factor, not a core component. CAVEAT: Double inference (yeast ortholog → human paralog) reduces confidence. Reason: Biochemical evidence from yeast shows TMA7 co-sediments with ribosomal fractions in an EDTA-dependent manner, indicating physical association with ribosomes. "Ribosome binding" appropriately describes transient association without implying TMA7 is a structural ribosomal component. Requires inference across orthology and paralogy; no direct human TMA7B binding evidence exists. Supporting Evidence: PMID:16702403 Immunoblotting revealed an EDTA-dependent cosedimentation with ribosomes in sucrose gradients for 11 candidate translation-machinery-associated (TMA) proteins file:human/TMA7B/TMA7B-deep-research-falcon.md TMA7 detected in 40S ribosomal fractions...The yeast TMA7 association with the 40S fraction and EDTA-sensitive ribosome co-sedimentation argues for a cytosolic, ribosome-associated localization during translation |
| GO:0002181 cytoplasmic translation | ISS PMID:16702403 Systematic identification and functional screens of uncharac... | NEW | Summary: This annotation is proposed based on yeast TMA7 ortholog evidence. Yeast tma7-null mutants show alterations in protein synthesis rates and polyribosome profiles, indicating a role in cytoplasmic translation [PMID:16702403]. CAVEAT: This involves a double inference (yeast TMA7 ortholog → human TMA7B paralog), so confidence is moderate. Neither human TMA7 nor TMA7B have been directly characterized experimentally. Reason: Strong functional evidence from yeast: tma7 deletion causes ~95% reduction in protein synthesis and altered polyribosome profiles. However, this annotation requires inference across both orthology (yeast→human) and paralogy (TMA7→TMA7B), which reduces confidence. TMA7 family conservation across eukaryotes (yeast, plant, mammal) supports the inference but direct human TMA7B evidence is lacking. Supporting Evidence: PMID:16702403 null yeast strains harboring deletions for several of the TMA genes had alterations in protein synthesis rates (TMA7 and TMA19), susceptibility to drugs that inhibit translation (TMA7), translation fidelity (TMA20), and polyribosome profiles (TMA7, TMA19, and TMA20) file:human/TMA7B/TMA7B-deep-research-falcon.md tma7 deletion → ~95% reduction in 35S-methionine incorporation, reduced polysomes vs monosomes, anisomycin resistance and slow growth — consistent with a role in translation (initiation/efficiency) |
| GO:0005829 cytosol | ISS PMID:16702403 Systematic identification and functional screens of uncharac... | NEW | Summary: Cytosolic localization is inferred from yeast TMA7 ortholog evidence. Yeast TMA7 shows EDTA-dependent cosedimentation with ribosomes in sucrose gradients. Plant TMA7 homolog also co-purifies with 80S cytosolic ribosomes. CAVEAT: Double inference (yeast ortholog → human paralog) reduces confidence; no direct human TMA7B localization data. Reason: Yeast TMA7 associates with cytosolic ribosomes, and plant TMA7 homolog co-purifies with 80S cytosolic ribosomes. Cytosolic localization is the parsimonious inference for TMA7B given conserved ribosome association across the TMA7 family. However, this requires inference across orthology and paralogy without direct human evidence. Supporting Evidence: PMID:16702403 Immunoblotting revealed an EDTA-dependent cosedimentation with ribosomes in sucrose gradients for 11 candidate translation-machinery-associated (TMA) proteins file:human/TMA7B/TMA7B-deep-research-falcon.md The yeast TMA7 association with the 40S fraction and EDTA-sensitive ribosome co-sedimentation argues for a cytosolic, ribosome-associated localization during translation |
| GO:0022627 cytosolic small ribosomal subunit | ISS PMID:16702403 Systematic identification and functional screens of uncharac... | NEW | Summary: This annotation is proposed based on yeast TMA7 ortholog evidence. Yeast TMA7 shows EDTA-dependent cosedimentation with ribosomes [PMID:16702403], and the deep research indicates specific association with the 40S ribosomal subunit. CAVEAT: Lower confidence due to (1) double inference chain (yeast ortholog → human paralog), and (2) TMA7 transiently associates with ribosomes rather than being a stable component - "colocalizes_with" may be more appropriate than "located_in". Reason: Biochemical evidence from yeast shows TMA7 co-sediments with 40S ribosomal fractions. EDTA sensitivity indicates association with assembled ribosomes. However, TMA7 is an associated factor, not a core ribosomal component, so this annotation may overstate the relationship. Direct human TMA7B evidence is lacking. Supporting Evidence: PMID:16702403 Immunoblotting revealed an EDTA-dependent cosedimentation with ribosomes in sucrose gradients for 11 candidate translation-machinery-associated (TMA) proteins file:human/TMA7B/TMA7B-deep-research-falcon.md TMA7 detected in 40S ribosomal fractions...The yeast TMA7 association with the 40S fraction and EDTA-sensitive ribosome co-sedimentation argues for a cytosolic, ribosome-associated localization during translation |
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Download this section (compressed HTML)Q: What is the functional relationship and potential redundancy between human TMA7 and TMA7B? Do they have overlapping expression patterns or distinct tissue-specific roles?
Suggested experts: Andrew J. Link
Q: Does human TMA7B, like yeast TMA7, associate with the 40S ribosomal subunit in an EDTA-sensitive manner? What is its precise role in translation initiation versus elongation?
Suggested experts: Andrew J. Link
Q: Is TMA7B involved in ribosome quality control pathways in humans, similar to the connection observed between Tma7 levels and HBS1L/PELO/EDF1 in mammalian systems?
Suggested experts: Pankaj B. Agrawal
Experiment: Perform sucrose gradient fractionation of human cell lysates (e.g., HEK293, HeLa) with and without EDTA treatment. Use western blotting or mass spectrometry to detect TMA7B in ribosomal fractions. EDTA sensitivity would indicate association with assembled ribosomes rather than free subunits.
Hypothesis: Human TMA7B associates with the 40S ribosomal subunit similar to yeast TMA7.
Type: Biochemical fractionation
Experiment: Generate TMA7B knockdown (siRNA) or knockout (CRISPR) human cell lines. Measure global protein synthesis using 35S-methionine incorporation, SUnSET assay, or OP-puromycin labeling. Perform polysome profiling to assess effects on translation initiation (polysome to monosome ratio).
Hypothesis: TMA7B knockdown reduces global translation rates in human cells.
Type: Functional genomics
Experiment: Generate single and double knockouts/knockdowns of TMA7 and TMA7B. Compare phenotypes (cell viability, translation rates, polysome profiles) to assess redundancy. Test whether overexpression of one paralog rescues loss of the other.
Hypothesis: TMA7 and TMA7B have redundant functions in human cells.
Type: Genetic complementation
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